Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial.

BACKGROUND: Current guidelines recommend a target international normalized ratio (INR) range of 2.5 to 3.5 in patients with a mechanical mitral prosthesis. The Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) Mitral randomized controlled noninferiority trial assessed safety and efficacy of warfarin at doses lower than currently recommended in patients with an On-X (Artivion, Inc) mechanical mitral valve. METHODS: After On-X mechanical mitral valve replacement, followed by at least 3 months of standard anticoagulation, 401 patients at 44 North American centers were randomized to low-dose warfarin (target INR, 2.0-2.5) or standard-dose warfarin (target INR, 2.5-3.5). All patients were prescribed aspirin, 81 mg daily, and encouraged to use home INR testing. The primary end point was the sum of the linearized rates of thromboembolism, valve thrombosis, and bleeding events. The design was based on an expected 7.3% event rate and 1.5% noninferiority margin. RESULTS: Mean patient follow-up was 4.1 years. Mean INR was 2.47 and 2.92 (P <.001) in the low-dose and standard-dose warfarin groups, respectively. Primary end point rates were 11.9% per patient-year in the low-dose group and 12.0% per patient-year in the standard-dose group (difference, -0.07%; 95% CI, -3.40% to 3.26%). The CI >1.5%, thus noninferiority was not achieved. Rates (percentage per patient-year) of the individual components of the primary end point were 2.3% vs 2.5% for thromboembolism, 0.5% vs 0.5% for valve thrombosis, and 9.13% vs 9.04% for bleeding. CONCLUSIONS: Compared with standard-dose warfarin, low-dose warfarin did not achieve noninferiority for the composite primary end point. (PROACT Clinicaltrials.gov number, NCT00291525).

WITHDRAWN: Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Controlled Trial.

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Consequences of radial artery harvest: results of a prospective, randomized, multicenter trial.

IMPORTANCE: To date, no study has defined the consequences of radial artery harvest based on a large number of patients in a prospective randomized trial. OBJECTIVE: To compare pain at the harvest site and functional changes associated with harvesting the radial artery vs saphenous vein for coronary artery bypass grafting. DESIGN, SETTING, AND PARTICIPANTS: This study compares the consequences of radial artery harvest with saphenous vein harvest in patients undergoing elective coronary artery bypass grafting procedures in Veterans Affairs hospitals. MAIN OUTCOMES AND MEASURES: Eleven hospitals screened 6148 patients, of whom 751 were included in this trial. We analyzed 2 variables: pain at the harvest site as measured on a scale of 0 to 100 (least to most painful) and hand performance testing. Patients included in this analysis had radial artery only (n = 80) or saphenous vein only (n = 337) harvest. Pain score, grip strength, and dexterity were measured before surgery and at 3 and 12 months after surgery. We adjusted for pain scores of the nonharvested extremity, age, whether the patient underwent endoscopic vein harvesting, and comorbid health conditions (smoking history, type 2 diabetes mellitus, hypertension, and heart failure). RESULTS: There was a significant difference in change of pain score at 3 months from the preoperative baseline between radial artery and saphenous vein groups after adjusting for covariates (P < .001) but not at 12 months (P = .07). No significant changes occurred in grip strength or dexterity from preoperative baseline to 3 and 12 months after surgery (P > .05). CONCLUSIONS AND RELEVANCE: The radial artery group reported significantly more pain than the saphenous vein group 3 months after surgery; however, similar levels of pain were observed in both groups at 12 months after surgery. Grip strength and manual dexterity were not changed by radial artery harvesting at 3 and 12 months.

Effect of laughter on mood and heart rate variability in patients awaiting organ transplantation: a pilot study.

CONTEXT: Research shows that laughter has myriad health benefits, yet the medical community has not implemented it formally as a treatment. Patients awaiting organ transplantation have significant physical disabilities and are at risk for psychological distress. Attenuated heart rate variability (HRV) is a risk factor for a negative long-term outcome in some patients. OBJECTIVE: The study intended to evaluate the clinical utility of laughter yoga in improving psychological and physiological measures in outpatients awaiting organ transplantation. Positive results would indicate promising areas to pursue in a follow-up study. DESIGN: Six participants met for 10 sessions over 4 weeks. The research team measured each participant's heart rate, HRV, blood pressure (BP), and immediate mood before and after the laughter and control interventions. The team assessed participants' longer-term mood (anxiety and depression) at the study's initiation, after a no-treatment control week, and at the end of the study. SETTING: The study occurred at the Department of Surgery and Medicine at the University of Arizona Health Sciences Center, Tucson. PARTICIPANTS: Participants were patients awaiting transplants (three heart and three lung), two women and four men (ages 51-69 y). Participants had received no major surgery in the 3 months prior to the intervention, did not have a hernia or uncontrolled hypertension, and did not fall into the New York Heart Association function class 4. INTERVENTION: The 20-minute laughter intervention involved breathing and stretching exercises, simulated laughter (ie, unconditional laughter that is not contingent on the environment), chanting, clapping, and a meditation. The 20-minute control intervention involved the study's personnel discussing health and study-related topics with the participants. OUTCOME MEASURES: The research team measured BP, heart rate, and HRV and administered the Profile of Mood States, Beck Anxiety Inventory, and Beck Depression Inventory-II to evaluate immediate and longer-term mood. The team had planned quantitative statistical analysis of the data at the study's initiation but did not complete it because the number of enrolled participants was too low for the analysis to be meaningful. The team visually examined the data, however, for trends that would indicate areas to examine further in a follow-up study. RESULTS: Participants showed improved immediate mood (vigor-activity and friendliness) and increased HRV after the laughter intervention. Both the laughter and control interventions appeared to improve longer-term anxiety. Two participants awaiting a lung transplant dropped out of the study, and no adverse events occurred. CONCLUSION: This pilot study suggests that laughter yoga may improve HRV and some aspects of mood, and this topic warrants further research.

Effect of laughter yoga on mood and heart rate variability in patients awaiting organ transplantation: a pilot study.

CONTEXT: Research shows that laughter has myriad health benefits, yet the medical community has not implemented it formally as a treatment. Patients awaiting organ transplantation have significant physical disabilities and are at risk for psychological distress. Attenuated heart rate variability (HRV) is a risk factor for a negative long-term outcome in some patients. OBJECTIVE: The study intended to evaluate the clinical utility of laughter yoga in improving psychological and physiological measures in outpatients awaiting organ transplantation. Positive results would indicate promising areas to pursue in a follow-up study. DESIGN: Six participants met for 10 sessions over 4 weeks. The research team measured each participant's heart rate, HRV, blood pressure (BP), and immediate mood before and after the laughter and control interventions. The team assessed participants' longer-term mood (anxiety and depression) at the study's initiation, after a no-treatment control week, and at the end of the study. SETTING: The study occurred at the Department of Surgery and Medicine at the University of Arizona Health Sciences Center, Tucson. PARTICIPANTS: Participants were patients awaiting transplants (three heart and three lung), two women and four men (ages 51-69 y). Participants had received no major surgery in the 3 months prior to the intervention, did not have a hernia or uncontrolled hypertension, and did not fall into the New York Heart Association function class 4. INTERVENTION: The 20-minute laughter intervention involved breathing and stretching exercises, simulated laughter (ie, unconditional laughter that is not contingent on the environment), chanting, clapping, and a meditation. The 20-minute control intervention involved the study's personnel discussing health and study-related topics with the participants. OUTCOME MEASURES: The research team measured BP, heart rate, and HRV and administered the Profile of Mood States, Beck Anxiety Inventory, and Beck Depression Inventory-II to evaluate immediate and longer-term mood. The team had planned quantitative statistical analysis of the data at the study's initiation but did not complete it because the number of enrolled participants was too low for the analysis to be meaningful. The team visually examined the data, however, for trends that would indicate areas to examine further in a follow-up study. RESULTS: Participants showed improved immediate mood (vigor-activity and friendliness) and increased HRV after the laughter intervention. Both the laughter and control interventions appeared to improve longer-term anxiety. Two participants awaiting a lung transplant dropped out of the study, and no adverse events occurred. CONCLUSION: This pilot study suggests that laughter yoga may improve HRV and some aspects of mood, and this topic warrants further research.

Radial artery grafts vs saphenous vein grafts in coronary artery bypass surgery: a randomized trial.

CONTEXT: Arterial grafts are thought to be better conduits than saphenous vein grafts for coronary artery bypass grafting (CABG) based on experience with using the left internal mammary artery to bypass the left anterior descending coronary artery. The efficacy of the radial artery graft is less clear. OBJECTIVE: To compare 1-year angiographic patency of radial artery grafts vs saphenous vein grafts in patients undergoing elective CABG. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized controlled trial conducted from February 2003 to February 2009 at 11 Veterans Affairs medical centers among 757 participants (99% men) undergoing first-time elective CABG. INTERVENTIONS: The left internal mammary artery was used to preferentially graft the left anterior descending coronary artery whenever possible; the best remaining recipient vessel was randomized to radial artery vs saphenous vein graft. MAIN OUTCOME MEASURES: The primary end point was angiographic graft patency at 1 year after CABG. Secondary end points included angiographic graft patency at 1 week after CABG, myocardial infarction, stroke, repeat revascularization, and death. RESULTS: Analysis included 733 patients (366 in the radial artery group, 367 in the saphenous vein group). There was no significant difference in study graft patency at 1 year after CABG (radial artery, 238/266; 89%; 95% confidence interval [CI], 86%-93%; saphenous vein, 239/269; 89%; 95% CI, 85%-93%; adjusted OR, 0.99; 95% CI, 0.56-1.74; P = .98). There were no significant differences in the secondary end points. CONCLUSION: Among Veterans Affairs patients undergoing first-time elective CABG, the use of a radial artery graft compared with saphenous vein graft did not result in greater 1-year patency. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00054847.

Pediatric bridge to heart transplantation: application of the Berlin Heart, Medos and Thoratec ventricular assist devices.

BACKGROUND: Bridge to transplantation (BTT) is an accepted option when a donor heart is not available. Extensive clinical study has been done with BTT in the adult population, but comparatively fewer data are available in the pediatric population with regard to pulsatile devices. METHODS: Ten pediatric patients are presented, all of whom underwent BTT or recovery with pneumatic paracorporeal systems. The Berlin Heart bi-ventricular assist device (BVAD) was utilized in 1 patient, the Medos VAD in 4 patients (1 left ventricular assist device [LVAD], 3 BVADs) and the Thoratec VAD in 5 patients (3 BVADs, 2 LVADs). The pediatric population consisted of 3 females and 7 males. Mean age of the population was 7.4 years, weight 25 kg and body surface area (BSA) 0.88 m(2). Etiology for heart failure consisted of 4 viral, 3 congenital and 3 idiopathic cardiomyopathies. Before implant, all patients had evidence of progressive cardiac failure despite inotropic support, and 2 patients had been on extracorporeal membrane oxygenation (ECMO). Mean duration on the device was 34.3 days (8 to 107 days). RESULTS: Two patients suffered stroke and recovered without sequelae. Two patients died of ischemic stroke and 1 of sepsis. Seven patients survived (6 transplanted and 1 weaned) for a survival rate of 70% compared with survival for ECMO as BTT, which was 40% to 50%. All survivors had complications related to bleeding, thromboembolic events and infections. CONCLUSIONS: The Thoratec VAD can be placed in small patients with large hearts that can accommodate the available cannulas. The Berlin Heart and the Medos VAD have a selection of ventricles with small stroke volumes. All 3 systems can be used successfully in the pediatric population as BTT with better survival than with ECMO.

CardioWest total artificial heart in a moribund adolescent with left ventricular thrombi.

Bridge to transplant is a well-known strategy to enable patients with congestive heart failure to live until transplant. A 15-year-old boy with Beckers' muscular dystrophy and cardiomyopathy was accepted for heart transplantation. He suffered a cardiac arrest and was placed on extracorporeal membrane oxygenator. A paracorporeal biventricular assist device and a total artificial heart were considered for bridge to transplant. A CardioWest total artificial heart was chosen because of the patient's size. Multiple left ventricular thrombi were identified at the time of the ventriculectomy. The patient did well with the total artificial heart was transplanted and discharged home. The unknown presence of significant left ventricular thrombi raises the question of outcome with a paracorporeal ventricular assist device.

Cardiac replacement with a total artificial heart as a bridge to transplantation.

BACKGROUND: The CardioWest Total Artificial Heart orthotopically replaces both native cardiac ventricles and all cardiac valves, thus eliminating problems commonly seen in the bridge to transplantation with left ventricular and biventricular assist devices, such as right heart failure, valvular regurgitation, cardiac arrhythmias, ventricular clots, intraventricular communications, and low blood flows. METHODS: We conducted a nonrandomized, prospective study in five centers with the use of historical controls. The purpose was to assess the safety and efficacy of the CardioWest Total Artificial Heart in transplant-eligible patients at risk for imminent death from irreversible biventricular cardiac failure. The primary end points included the rates of survival to heart transplantation and of survival after transplantation. RESULTS: Eighty-one patients received the artificial-heart device. The rate of survival to transplantation was 79 percent (95 percent confidence interval, 68 to 87 percent). Of the 35 control patients who met the same entry criteria but did not receive the artificial heart, 46 percent survived to transplantation (P<0.001). Overall, the one-year survival rate among the patients who received the artificial heart was 70 percent, as compared with 31 percent among the controls (P<0.001). One-year and five-year survival rates after transplantation among patients who had received a total artificial heart as a bridge to transplantation were 86 and 64 percent. CONCLUSIONS: Implantation of the total artificial heart improved the rate of survival to cardiac transplantation and survival after transplantation. This device prevents death in critically ill patients who have irreversible biventricular failure and are candidates for cardiac transplantation.

Total artificial heart bridge to transplantation: a 9-year experience with 62 patients.

BACKGROUND: The SynCardia CardioWest total artificial heart (CardioWest TAH) is a biventricular, orthotopic, pneumatic, pulsatile blood pump driven by an external console. For each ventricle, the length of the blood-flow path is shorter and the inflow and outflow valves are larger than in any other bridge-to-transplant device, resulting in greater blood flow at smaller pre-load. Such a device should be optimal for bridging transplant candidates who have biventricular failure and for whom all other therapies have failed. METHODS: From January 1, 1993, to April 1, 2002, we prospectively studied 62 consecutive CardioWest TAH implant recipients to document safety and efficacy in bridge to transplantation. We used multisystem monitoring and multidrug therapy for anti-coagulation in 58 patients starting September 1, 1994. RESULTS: Before implantation, patients were critically ill with biventricular heart failure. Mortality in this group from the time of implantation until transplantation was 23%. Causes of death during device support included multi-organ failure (6), sepsis (3), and valve entrapment (2). Forty-eight patients underwent transplantation (77%). Forty-two survived to hospital discharge (68% of the total, 88% of those undergoing transplantation). Adverse events included bleeding (20%), device malfunction (5%), fit complications (3%), mediastinal infections (5%), visceral embolus (1.6%), and stroke during support (1.6%). The linearized stroke rate was 0.068 events per patient-year. CONCLUSIONS: Sixty-eight percent of critically ill transplant candidates for whom medical therapy failed were bridged to transplantation with the CardioWest TAH and survived long-term. Most deaths that occurred during device support were related to pre-implant problems. Infection and stroke were rare events. Therefore, we recommend the CardioWest TAH as the biventricular bridge-to-transplant device of choice.

Predictors of cognitive decline following coronary artery bypass graft surgery.

BACKGROUND: A significant number of patients develop cognitive impairment that persists for months following coronary artery bypass grafting (CABG) surgery. Our objectives were to identify patient-related risk factors, processes of care, and the occurrence of any perioperative complications associated with cognitive decline. METHODS: Nine hundred thirty-nine patients enrolled in the Processes, Structures, and Outcomes of Care in Cardiac Surgery study undergoing CABG-only surgery at 14 Veterans Administration medical centers between 1992 and 1996 completed a short battery of cognitive tests at baseline and 6-months post-CABG. The composite cognitive score was based on the sum of errors for each individual item in the battery. Multiple linear regression analyses were used to identify independent predictors of the 6-month composite cognitive score. RESULTS: In multivariable analyses, patient characteristics associated with cognitive decline included cerebrovascular disease (p = 0.009), peripheral vascular disease (p = 0.007), history of chronic disabling neurologic illness (p = 0.016), and living alone (p = 0.049), while the number of years of education (p = 0.001) was inversely related to cognitive decline. After adjustment for baseline patient risk factors, the presence of any postoperative complication(s) (p = 0.001) was also associated with cognitive decline while cardiopulmonary bypass time (p = 0.008) was inversely related to cognitive decline. CONCLUSIONS: Patients with noncoronary manifestations of atherosclerosis, chronic disabling neurologic illness, or limited social support are at risk for cognitive decline after CABG surgery. In contrast, more years of education were associated with less cognitive decline. Preoperative assessment of risk factors identified in this study may be useful when counseling patients about the risk for cognitive decline following CABG surgery.

Relationship between processes of care and coronary bypass operative mortality and morbidity.

BACKGROUND: Information is limited regarding the effects of processes of care on cardiac surgical outcomes. Correspondingly, many recommended cardiac surgical processes of care are derived from animal experiments or clinical judgment. This report from the VA Cooperative Study in Health Services, "Processes, Structures, and Outcomes of Cardiac Surgery," focuses on the relationships between 3 process groups (preoperative evaluation, intraoperative care, and supervision by senior physicians) and a composite outcome, perioperative mortality and morbidity. METHODS: Data on 734 risk, process, and structure variables were collected prospectively on 3,988 patients who underwent coronary artery bypass grafting at 14 VA medical centers between 1992 and 1996. Data reduction was accomplished by examining data completeness and variation across sites and surgeon, using previously published data and clinical judgment. We then applied multivariable logistic regression to the 39 remaining processes of care to determine which were related to the composite outcome after adjusting for 17 patient-related risk factors and controlling for intraoperative complications. RESULTS: Our first analysis showed several measures of operative duration, the use of inotropic agents, transesophageal echo, lowest systemic temperature, and hemoconcentration/ultrafiltration, to be powerful predictors of the composite outcome. Because the use of inotropic agents and operative duration may be related to an intermediate outcome (eg, intraoperative complications), we performed a second analysis omitting these processes. The use of intraoperative transesophageal echo and hemoconcentration/ultrafiltration remained significantly associated with an increased risk of an event (odds ratios 1.60 and 1.36, respectively). CONCLUSIONS: Our results viewed in the context of past studies suggest the possibility that inotropic use, TEE, and hemoconcentration/ultrafiltration may have adverse effects on operative outcome. Further evaluation of these processes of care using observational data, as well as randomized trials when feasible, would be of interest.

Successful management of empyema in a patient with a total artificial heart.

A description of successful management of a patient who developed an empyema as a postoperative complication following the insertion of a CardioWest total artificial heart (TAH) as a bridge to cardiac transplantation is presented. By using traditional methods of management, the patient recovered and went on to transplant.

Multiple giant aneurysms of coronary arteries.

Multiple giant aneurysms of the coronary arteries occur extremely rarely and are usually associated with Kawasaki disease in children. A 53-year-old man with multiple giant coronary artery aneurysms was treated successfully by aortocoronary bypass grafting.

Standard versus fiberoptic pulmonary artery catheterization for cardiac surgery in the Department of Veterans Affairs: a prospective, observational, multicenter analysis.

BACKGROUND: Controversy exists regarding the utility of continuous monitoring of mixed venous oxygen saturation (STvo2) during cardiac surgery. During a multicenter, prospective, observational study in the Department of Veterans Affairs (Cooperative Study #5), frequency of use of standard pulmonary artery catheterization (PAC) and STvo2-PAC was recorded. Here the authors relate these data to clinical outcomes. METHODS: Logistic and Cox regression models evaluating the association of PAC type with mortality, one or more postoperative complications, cardiac complications, time to extubation, and intensive care unit length of stay were constructed. The number of thermodilution cardiac outputs and arterial blood gas analyses performed in the first 24 h postoperatively were compared. RESULTS: Data from 3,265 patients undergoing myocardial revascularization (81.7%) or valve replacement-repair (18.3%) were considered. STvo2-PAC was used in 49% and PAC in 51% of patients. In the 14 hospitals, STvo2-PAC was used in all patients in four, in some patients in four, and never in six. No association of STvo2-PAC use with outcome were observed aside from unexplained hospital level effects. A small but statistically significant reduction in the number of arterial blood gas analyses (8 +/- 3 vs. 10 +/- 4, P < 0.0001, STvo2-PAC vs. PAC, respectively) and thermodilution cardiac outputs (14 +/- 8 vs. 15 +/- 9, P < 0.0001, STvo2-PAC vs. PAC, respectively) was observed with use of STvo2-PAC. CONCLUSIONS: Despite higher cost, STvo2-PAC was commonly used in this cohort. Our analysis failed to detect associations with improved outcomes aside from a small reduction in resource utilization. The precise role of STvo2-PAC remains uncertain.

Comparison of postoperative comlications between saphenous vein and IMA grafts to left anterior descending coronary artery.

Considerable controversy exists regarding relative morbidity associated with the saphenous vein graft (SVG) and internal mammary artery (IMA) graft in patients undergoing myocardial revascularization. As a part of the cooperative study on use of antiplatelet drugs for graft patency, operative and postoperative data were prospectively collected on 1,150 patients who underwent either SVG (n = 656) or IMA anastomosis (n = 494) to the left anterior descending coronary artery. There were no differences in baseline characteristics of patients, distribution of randomization among treatment groups, and total number of distal anastomoses performed between the two groups. The aortic cross-clamp time, cardiopulmonary bypass duration, operative time, and chest tube drainage were greater (p = 0.0001) in the patients with IMA grafts compared with SVG. However, there was no difference in the operative mortality rate, the amount or blood and blood products received, the reoperation rate for control of postoperative bleeding, and incidence of wound complications between the two groups. The early and 1-year patency rates for the IMA were slightly but not significantly better than the SVG patency rates (92.8% versus 90.1% for 1-year patency; p = 0.309). In conclusion, use of IMA is associated with a longer operative time as well as increased postoperative bleeding compared with the SVG. It, however, does not increase operative mortality or postoperative morbidity.